ORCID ID

Contact details

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

15598

Study information

Scientific title

Bevacizumab in combination with metronomic dose temozolomide in patients with relapsed high grade gliomas

Acronym

AVATAR

Study hypothesis

The change of chemotherapeutic temozolomide schedule from conventional to metronomic treatment may overcome temozolomide resistance in patients with recurrent glioma without any major toxicity. Administration of angiogenesis inhibitor bevacizumab leads to normalisation of glioma tumour blood vessels, during a period of at least 28 days. During this normalisation window, administration of acombination therapy is thought to be most effective. Therefore we combine bevacizumab with metronomic dose temozolomide treatment. The PFS6 (Progression Free Survival at 6 months) is about 9% in this patient group under the old treatment regimen. We expect a PFS6 of about 30% with the combination of bevacizumab and temozolomide. Therapy regimen will continue after six months.

Study design

Primary study design

Interventional

Secondary study design

Non randomised controlled trial

Trial setting

Not specified

Trial type

Not Specified

Patient information sheet

Condition

Relapsed glioma

Intervention

The effects of the combination of Bevacizumab (10 mg every three weeks, intravenously [iv]) with daily Temozolomide (50 mg/m^2, orally) will be compared with historical data of a matched patient group. The MRI effects of (co-) administration of dexamethasone (daily 3 dd 4 mg, orally) will be examined during the first 20 days of the experiment.

Intervention type

Drug

Phase

Not Specified

Drug names

Bevacizumab, temozolomide

Primary outcome measure

Main study parameters/endpoints: The Progression Free Survival at 6 months (PFS6) is the main study parameter. This is about 9% in this patient group under the old treatment regimen. We expect a PFS6 of about 30% with the combination of bevacizumab and temozolomide. Therapy regimen will continue after six months.

Overall trial start date

13/02/2007

Overall trial end date

01/02/2009

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Patients present with histologically confirmed diagnosis of intracranial recurrent high grade glial tumour (World Health Organisation [WHO] grade IV). Patients may be entered based on local pathology from the original tumour specimen2. Patients must have evidence of tumour progression following radiation and chemotherapy as measured by Magnetic Resonance Imaging (MRI) (MRI-0 at presentation)3. Patients may have received up to two prior chemotherapy regimens (with concurrent radiotherapy)4. Patients may have undergone prior surgical resection and will be eligible if recovered from the effects of surgery5. Patients must have adequate organ function, including the following:5.1. Adequate bone marrow reserve: Absolute Neutrophil Count (ANC) greater than 1.5 x 10^9/L, platelet count greater than 100 x 10^9/L, and haemoglobin greater than g/dL (6.21 mmol/L)5.2. Hepatic: total bilirubin less than two times the Upper Limit of Normal (ULN); Alkaline Phosphatase (ALP), Aspartate Transaminase (AST), and Alanine Transaminase (ALT) less than 3 x ULN5.3. Renal: serum creatinine less than 1.5 ULNThese tests must be performed less than five days prior to enrolment. Eligibility for haemoglobin count may be reached by transfusion6. Patients must have a Karnofsky Performance Score greater than 70%7. Patients must be greater than 18 years of age, with a life expectancy of greater than eight weeks8. Patient compliance and geographic proximity that allow for adequate follow up is required9. Male and female patients with reproductive potential must use an approved contraceptive method, if appropriate (for example, Intrauterine Device [IUD], birth control pills, or barrier device) during and for three months after discontinuation of study treatment. Women with childbearing potential must have a negative serum pregnancy test less than three days prior to study enrolment10. Signed informed consent from the patient or legal representative is required

Participant type

Patient

Age group

Not Specified

Gender

Both

Target number of participants

30

Participant exclusion criteria

1. Patients with inability to comply with protocol or study procedures (for example, an inability to swallow tablets)2. Patients who have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry3. Patients receiving EIAEDs (Enzyme-Inducing Anti-Epileptic Drugs). Patients must discontinue EIAEDs greater than 14 days prior to study enrolment. The investigator may prescribe non-EIAEDs4. Patients receiving any other anticancer therapy, any anticoagulant therapy5. Patients with serious concomitant systemic disorders (for example, active infection or abnormal electrocardiogram indicative of cardiac disease) that, in opinion of the investigator, would compromise the safety of the patient and his/her ability to complete the study6. Patients with prior thrombo-embolic events